dbSNP rs2295774: SEC31B:p.Ser332Ala (chr10-100506090-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015490.4(SEC31B):c.994T>G(p.Ser332Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,614,028 control chromosomes in the GnomAD database, including 36,687 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.17 ( 2606 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34081 hom. )

Consequence

SEC31B
NM_015490.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.43

Variant links:

Genes affected

SEC31B (HGNC:23197): (SEC31 homolog B, COPII coat complex component) This gene encodes a protein of unknown function. The protein has moderate similarity to rat VAP1 protein which is an endosomal membrane-associated protein, containing a putative Ca2+/calmodulin-dependent kinase II phosphorylation site. [provided by RefSeq, Jul 2008]

SEC31B links:

ENSG00000255339 (HGNC:):

ENSG00000255339 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018028915).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEC31B	NM_015490.4 link	c.994T>G	p.Ser332Ala	missense_variant	Exon 9 of 26	ENST00000370345.8	NP_056305.1	Q9NQW1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEC31B	ENST00000370345.8 link	c.994T>G	p.Ser332Ala	missense_variant	Exon 9 of 26	1	NM_015490.4	ENSP00000359370.3		Q9NQW1-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26461

AN:

152072

Hom.:

2604

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0864

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.168

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.229

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.183

GnomAD3 exomes

AF:

0.197

AC:

49510

AN:

251288

Hom.:

5247

AF XY:

0.201

AC XY:

27349

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0850

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.195

Gnomad EAS exome

AF:

0.143

Gnomad SAS exome

AF:

0.223

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.209

GnomAD4 exome

AF:

0.213

AC:

311056

AN:

1461838

Hom.:

34081

Cov.:

AF XY:

0.214

AC XY:

155775

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0783

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.199

Gnomad4 EAS exome

AF:

0.178

Gnomad4 SAS exome

AF:

0.227

Gnomad4 FIN exome

AF:

0.233

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.174

AC:

26456

AN:

152190

Hom.:

2606

Cov.:

AF XY:

0.176

AC XY:

13083

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.0863

Gnomad4 AMR

AF:

0.168

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.230

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.218

Gnomad4 OTH

AF:

0.181

Alfa

AF:

0.203

Hom.:

6076

Bravo

AF:

0.166

TwinsUK

AF:

0.217

AC:

804

ALSPAC

AF:

0.214

AC:

826

ESP6500AA

AF:

0.0772

AC:

340

ESP6500EA

AF:

0.220

AC:

1888

ExAC

AF:

0.198

AC:

24034

Asia WGS

AF:

0.186

AC:

646

AN:

3478

EpiCase

AF:

0.208

EpiControl

AF:

0.210

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Pathogenic

0.92

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.011

Polyphen

1.0

Vest4

0.29

MPC

0.21

ClinPred

0.045

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over